This is a critical time for HIV prevention. Beginning in 2010, results from randomized clinical trials showed that HIV pre-exposure prophylaxis (PrEP) is a safe and efficacious method of reducing HIV acquisition. However, despite increasing knowledge about and use of PrEP nationally, HIV continues to have disproportionate impact among men and transgender persons who have sex with men (MSM/TG), with methamphetamine (meth)- users being at particularly high risk. Despite apparent high levels of PrEP knowledge and exceptional insurance and medication coverage, few meth-users in Western WA have enrolled in local PrEP programs. Our preliminary work with meth-using MSM/TG has identified both traditional barriers to PrEP and barriers specific to meth users, including competing priorities (e.g., getting high); lack of regularity in daily schedules leading to difficulties complying with appointments and medication adherence; and concomitant wellness and social concerns, notably depression and meth-related stigma. Additional work is needed to develop new strategies to increase PrEP uptake and support persistence and adherence among meth-using MSM/TG. The project proposed in this Clinical Trial Planning Grant (R34) will develop and provide preliminary data for peer navigation and theory-based text messaging interventions for meth-using MSM/TG and will provide support for a future phase III clinical trial by establishing the research team, developing tools for data collection and cost-effective analyses, and finalizing the study protocol and manual of procedures. Formative work described in Aim #1 will expand on existing collaborations between academic researchers, public health, CBOs in Western WA serving meth-using MSM/TG, two community-based PrEP clinics, and other key partners. In Aims #2 and #3, we will conduct a pilot RCT with 40 meth-using MSM/TG initiating PrEP to evaluate the acceptability and feasibility of each of the interventions. In doing so, we will collect preliminary data to assess the ability of our interventions to shape PrEP into effective HIV prevention for meth-using MSM/TG. This application's strengths include a focus on several topics that have been sought in order to improve the HIV PrEP Cascade. These include the development and pilot testing of interventions to improve PrEP care engagement and retention among individuals at substantial risk for HIV infection, as well as interventions to support PrEP medication adherence and persistence. Employing a research team with substantive expertise in PrEP both nationally and internationally, the development of other peer navigation and adherence counseling interventions, HIV testing and prevention programming, substance use interventions, and cost-effectiveness analysis, this collaboration will work to directly inform an efficacy trial to be proposed in a future application and thus maximize PrEP's ability to reduce new infections among the persons at highest risk of HIV acquisition.